Black women experience a disproportionate burden of pre-menopausal breast cancer for reasons that remain unknown and understudied. We are in a new era of medicine where genetic markers are being used to make clinical management decisions, yet there is paucity of data on how the genetic alterations in tumors from Black women interact with their socio-cultural environment and how these interactions underlie the poor clinical outcomes observed in Black women. Our long-term goal in the Chicago Center for Interdisciplinary Health Disparities Research is to fill these gaps by assembling a large cohort of breast cancer cases who are African American women from the South Side of Chicago and Nigerian women. This will be an invaluable resource for generating hypotheses about the biology and psychosocial determinants of aggressive breast cancer that disproportionately affects Black women. One hypothesis integrating this Center grant is that breast cancer is more prevalent and aggressive in a subset of Black women because the threats and demands in their lives outweigh their social supports. To test this hypothesis, we propose the following aims: 1) assess the relationship of hypermethylafion of the BRCA1 and ER promoters with the patients' demographics, family and reproductive histories, environmental exposures, loneliness, hypervigilance and Social supports/demands 2) assess the role of HER2/neu and MYC as cooperating oncogenes in the tumors from Black women; 3) examine gene expression profiles in a subset of patients to determine whether there are "Black-specific" gene expression profiles. A second and related outcome that we believe to be more likely is that there are not any "race specific" profiles, but that the proportion of tumors within a given subtype might be different. Based upon the epidemiological finding that Blacks show a higher proportion of ER-negative tumors, we would predict that they would show higher numbers of basal-like tumors that correlate with varying degrees of social isolation and hypervigilance. Conceptually, this project is linked with Projects 1 and 4, in which animal models of health disparities in human breast cancer will be used to identify mechanisms by which social isolation and hypervigilance increase the incidence, rate of development, and aggressiveness of murine mammary tumors. In collaboration with project 3 (Participatory Research), we will use multiple psychosocial measures at several levels of analysis: neighborhood, sociat networks and family as well as individual experience and psychological states to quantify the risk of breast cancer specific to Black women.